UTIs (Dr. Withey)
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What are the 5 locations where UTIs are most common?
- 1. Kidney (Pyelonephritis)
- 2. Ureter (Ureteritis)
- 3. Bladder (Cystitis)
- 4. Prostate (Prostatitis)
- 5. Urethra (Urethritis)
Which UTIs are located in the lower UT?
Which UTIs are located in the upper UT?
- Intra-renal abscess
- Perinephric abscess
What pathogen(s) are the most likely causative agent(s) for uncomplicated UTIs?
What pathogen(s) are the most likely causative agent(s) for complicated UTIs?
- E. coli
- S. saprophyticus
- Klebsiella spp.
- and many others!
What is the clinical presentation for lower UTIs (cystitis)?
- Urinary urgency and frequency
- bladder fullness
- hemorrhagic cystitis (10% of cases)
What is the clinical presentation for lower UTIs (prostatitis)?
- pain and tenderness in lower back and suprapubic area
- perirectal area and testicles
- acute onset
- more severe symptoms
- bacteremia and hematuria
What is the clinical presentation for upper UTIs (pyelonephritis)?
- cystitis symptoms (Dysuria, Urinary urgency and frequency, bladder fullness, hemorrhagic cystitis (10% of cases))
- fever, sweating
- flank pain
- dehydration, hypotension
- septicemic shock
What are th pathogenic mechanisms for UTIs?
- entry by ascent from urethra
- often caused by poor hygiene
- adherence to host epithelium - adhesins, pili, and polysaccharides
What E. coli virulence factors contribute to UTIs?
- P-pili associated with pyelonephritis (PAP) - mediate binding to uroepithelial cells via glycosphingolipids, and also binds to RBC leading to hemagglutination; inhibits phagocytosis, mannose insensitive, induces interleukin and PMN infiltration to bladder
- Type 1 pili - agglutinates RBC and mediates binding, mannose sensitive, genetic switch
- Type S fimbriae (SfaI, SfaII) - agglutinates RBCs, mannose insensitive, causes both cystitis AND pyelonephritis, binds sialic acids on glycoproteins, assoc. with neonatal meningitis and bacteremia
- afimbrial adhesins (AfaD, AfaE) - adhesion to uroepithelium and internalization
- toxins - hemolysin, needs iron for growth; cytotoxin necrotizing factor type I - apoptosis of uroepithelium
- LPS - endotoxin, stimulates proinflammatory cytokine release
- K antigen - capsule, antiphagocytic
What S. saprophyticus virulence factors contribute to UTIs?
- S. saprophyticus surface-associated protein
- hemagglutinin/fibronectin-binding protein
- hemolysin - not found in all uropathogenic strains
- urease - toxic to bladder tissue, can form stones which can obstruct UT and impede urinary flow
What K. pneumoniae virulence factors contribute to UTIs?
- Type 1 fimbriae - mannose sensitive hemagglutininType 3 fimbriae - mannose resistant hemagglutininCapsule - bilayer, antiphagocytic
- LPS - serum-resistance, O antigen
- Urease - stone formation
What P. mirabilis virulence factors contribute to UTIs?
- Adhesins - Mannose-resistant Proteus-like (MR/P), hemagglutinin
- Proteus mirabilis fimbriae (PMF) - not a hemmaglutinin
- flagella - motility
- urease - foul smelling, ammonia; stone formation
- HpmA hemolysin - potent, cytotoxic
What Enterococcus spp. virulence factors contribute to UTIs?
- Aggregation substance (Asa1) - conjugal plasmid exchange between cells, adhesion to eukaryotic cells expressing integrins
- cytolysin - kills RBCs, release iron for growth
- sex pheromones - plasmid acquisition, triggers immune response
What are the host factors involved in UTIs?
- mannose receptors on uroepithelial cells
- women with recurrent UTI have more mannose receptors
- certain blood groups are more prone to have recurrent UTIs
What are the 5 host protective mechanisms to help fight UTIs?
- normal flora
- sloughing of uroepithelium
- high osmolality, low pH of urine
- insignificant immune defense
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